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421 results about "Autophagy" patented technology

Autophagy (or autophagocytosis) (from the Ancient Greek αὐτόφαγος autóphagos, meaning "self-devouring" and κύτος kýtos, meaning "hollow") is the natural, regulated mechanism of the cell that removes unnecessary or dysfunctional components. It allows the orderly degradation and recycling of cellular components.

Barrier repair composition for activating cell energy and application thereof

The invention relates to a barrier repair composition for activating cell energy and application thereof, the composition comprises the following components: nicotinamide, a wheat germ extract, oat beta-glucan and a golden camellia flower extract, the four components synergistically form a full-link barrier repair system of energy supply (nicotinamide)-autophagy cleaning (wheat germ extract)-structure strengthening (beta-glucan)-oxidation defense (camellia nitidissima extract), the limitation that a traditional skin care product singly supplements lipid or resists oxidation is broken through, lipid dynamic balance is rebuilt from the root of cell metabolism, and the skin care product has the advantages that the skin care effect is good; and certain skin smoothing and anti-aging effects are achieved.
Owner:N O D TOPIA (GUANGZHOU) BIOTECHNOLOGY CO LTD

Lactiplantibacillus plantarum 24 and its applications

The present invention provides a Lactiplantibacillus plantarum ( Lactiplantibacillus plantarum ), strain 24, which is deposited in the China General Microbiological Culture Collection Center, deposit number: CGMCC No. 31278. The Lactiplantibacillus plantarum 24 of the present invention can secrete sphingomyelinase to promote the production of ceramide in HaCaT cells; Lactiplantibacillus plantarum 24 or its metabolite or its lysate can up-regulate the expression of key enzymes in the sphingomyelinase and / or ceramide synthesis pathway of skin cells, repair the skin barrier; down-regulate the expression of pro-inflammatory cytokines, inhibit autophagy, and has a good anti-inflammatory effect; at the same time, it also has good antioxidant and whitening effects. The Lactiplantibacillus plantarum 24 or its metabolite or its cell lysate of the present invention can be used in the preparation of products having the above-mentioned effects or functions.
Owner:TIANJIN UNIV OF SCI & TECH +1

Application of tea exosome in preparation of medicine for improving skin pigmentation

The invention relates to application of a tea exosome in preparation of a medicine for improving skin pigmentation, the tea exosome is creatively extracted and purified, and the tea exosome can effectively inhibit proliferation of melanoma cells and inhibit expression of melanin generation related protein by scavenging free radicals and inhibiting tyrosinase activity, so that the effect of improving skin pigmentation is achieved. The intracellular melanin removal is promoted. In a mouse in-vivo experiment, after the tea exosome is applied, it is observed that the skin epidermis thickness of a mouse is reduced, the dermis thickness is increased, collagen arrangement is tighter and more ordered, the content is increased, and meanwhile generation of inflammatory factors is reduced. The tea exosome can significantly increase the content of a melanin autophagy key factor LC3B and reduce the content of P62 to promote melanin autophagy, and has good percutaneous infiltration capacity, thereby playing a role in improving skin pigmentation.
Owner:FUJIAN MEDICAL UNIV UNION HOSPITAL

Enhancing autophagy or increasing longevity by administration of urolithins

Disclosed are methods, compounds, and compositions useful for increasing autophagy and promoting longevity. The methods, compounds, and compositions relate to urolithins and urolithin precursors and use thereof. Certain urolithins are represented by Formula I, while certain urolithin precursors are represented by Formula IV. The urolithin may be urolithin A, urolithin B, urolithin C, or urolithin D. The urolithin precursor may be ellagic acid or an ellagitannin. The methods include in vivo, ex vivo, and in vitro uses of the compounds and compositions.
Owner:AMAZENTIS SA

Compositions and methods using one or more autophagy-inducing amino acids to potentiate musculoskeletal effect of one or more anabolic amino acids

A method of potentiating musculoskeletal effect of one or more anabolic amino acids in an individual in need thereof can include administering to the individual in need thereof a composition containing the one or more anabolic amino acids, the composition also containing one or more autophagy-inducing amino acids in a total amount effective for the composition to be at least neutral regarding autophagy. In another aspect, a method of overcoming one or more negative effects of one or more anabolic amino acids by preventing degenerative processes related to loss of autophagy can include administering to an individual in need thereof a composition containing the one or more anabolic amino acids, the composition further containing the one or more autophagy-inducing amino acids in a total amount effective for the composition to be at least neutral regarding autophagy.
Owner:SOCIETE DES PRODUITS NESTLE SA

Learning concentration training system based on brain wave analysis

The invention provides a learning concentration training system based on brain wave analysis, and relates to the field of electroencephalogram signal processing. Comprising the following steps: calculating a user concentration degree and a theta / beta wave energy ratio in real time through an electroencephalogram signal acquisition module, and triggering subsequent processing when the ratio exceeds a threshold value; the quantum coding module converts the electroencephalogram signal into a discrete quantum state carrying a recursive coding chain, and feeds back the discrete quantum state to the reverse interference engine module to generate a chaotic waveform, and the chaotic waveform is reversely injected to form closed-loop interference; the electrode autophagy module dynamically generates electrode topological parameters based on a theta / beta wave steady state activation autophagy protocol and feeds back the electrode topological parameters through a hypergraph network; the kink operation module maps the electroencephalogram energy into a three-dimensional kink during concentration breakthrough and cuts off a low-energy branch, and released energy is converted into an autophagy triggering probability; the compatibility of a recursive chain and historical data is verified through a paradox constraint and a clock synchronization module, a negative probability flow is adjusted to a chaos stability domain, and multi-module synchronization is achieved through a non-von Noremann clock tree.
Owner:SHIHEZI UNIVERSITY

Preparation and application of NCOA4-targeting benzofuran [2, 3-b] pyridine derivative

The invention belongs to the technical field of medicinal chemistry, and discloses a preparation method and application of a benzofuran [2, 3-b] pyridine derivative of a targeted nuclear receptor co-activator 4 (NCOA4). The derivative has a structural general formula as shown in the following formula (I), wherein R1, R2 and R3 substituent groups can be combined at will. The compounds are combined with NCOA4 to interfere the cell iron autophagy process and effectively inhibit the ferroptosis of various cells induced by RSL3 or Erastin. Particularly, the binding affinity of the compound 4k and NCOA4 is optimal (Kd is equal to 0.78 mu M), and the compound 4k has remarkable ferroptosis inhibition activity and can be used for research and development of medicines for ferroptosis-related diseases. # imgabs0 #
Owner:CHONGQING MEDICAL UNIVERSITY

Enhancing autophagy or increasing longevity by administration of urolithins or precursors thereof

Disclosed are methods, compounds, and compositions useful for increasing autophagy and promoting longevity. The methods, compounds, and compositions relate to urolithins and urolithin precursors and use thereof. Certain urolithins are represented by Formula I, while certain urolithin precursors are represented by Formula IV. The urolithin may be urolithin A, urolithin B, urolithin C, or urolithin D. The urolithin precursor may be ellagic acid or an ellagitannin. The methods include in vivo, ex vivo, and in vitro uses of the compounds and compositions.
Owner:AMAZENTIS SA

Recombinant VII type collagen with firming and anti-wrinkle effects

The invention discloses a recombinant VII type collagen as well as a preparation method and application thereof. The recombinant VII type collagen is obtained by repeating a short amino acid sequence GLPGAKGEKGAP for a plurality of times. The secretion yield of the recombinant VII type collagen in a commercial pichia pastoris expression system can be up to about 17.3 g / L, the extracellular secreted protein is basically not degraded in the fermentation process, the purity can reach 90% or above through simple ultrafiltration and decoloration, and industrial mass production can be achieved; and the recombinant VII type collagen has better biological activities of promoting autophagy, improving an endoplasmic reticulum stress state, promoting collagen secretion and inhibiting matrix metalloproteinase from degrading collagen, and shows good tightening and anti-wrinkle effects.
Owner:XIAN GIANT BIOGENE TECH CO LTD

Adipose-derived stem cell exosome compound loaded with silver nanoparticles and application of adipose-derived stem cell exosome compound

The invention discloses an adipose-derived stem cell exosome compound loaded with silver nanoparticles and application of the adipose-derived stem cell exosome compound loaded with the silver nanoparticles, and ADSC-Exos loaded with the silver nanoparticles is developed by integrating AgNPs into an exosome of ADSCs. In vivo, the Exo-AgNPs can accelerate healing of infected wounds by reducing bacterial colonization and promoting collagen deposition, angiogenesis and M2 type macrophage polarization. In vitro, the Exo-AgNPs activates the functions of fibroblasts and vascular endothelial cells, and shows an excellent antibacterial property. In addition, the Exo-AgNPs induces polarization of M2 type macrophages and inhibits secretion of proinflammatory cytokines by activating autophagy. The results show that Exo-AgNPs is expected to become an ideal biological material for treating infected wounds.
Owner:TONGJI HOSPITAL ATTACHED TO TONGJI MEDICAL COLLEGE HUAZHONG SCI TECH

Umbilical cord mesenchymal stem cell exosome as well as preparation method and application thereof

The invention relates to the technical field of biomedicine, in particular to an umbilical cord mesenchymal stem cell exosome and a preparation method and application thereof.The umbilical cord mesenchymal stem cell exosome is derived from umbilical cord mesenchymal stem cells expressing S100g-MTOR binding domain fusion protein and can inhibit excessive autophagy through an S100g / MTOR signal channel, and therefore intestinal mucosal barrier damage caused by antibiotics is relieved. The preparation method comprises the following steps: constructing an expression vector, transfecting and screening a stable expression cell strain, performing serum-free culture, collecting a culture supernatant, purifying the exosome and the like. The exosome disclosed by the invention can be used for preparing a medicine for treating antibiotic-related intestinal mucosal barrier injury, has the advantages of strong targeting property, definite action mechanism, remarkable curative effect and the like, and provides a new choice for preventing and treating antibiotic-related intestinal adverse reactions.
Owner:AFFILIATED HOSPITAL OF JINING MEDICAL UNIV

Autophagy extracellular vesicles capable of swallowing viruses as well as preparation method and application of autophagy extracellular vesicles

The invention relates to autophagy extracellular vesicles capable of swallowing viruses as well as a preparation method and application of the autophagy extracellular vesicles, and relates to the technical field of biological medicines. The preparation method of the high-purity autophagy extracellular vesicles is provided for the first time, the purity of the high-purity autophagy extracellular vesicles exceeds 85%, and the high-purity autophagy extracellular vesicles are rich in various protein markers. CVB4 virus is used for infecting the autophagy extracellular vesicles, it is found that compared with common extracellular vesicles, the autophagy extracellular vesicles contain complete CVB4 virus particles, and the virus particles carried by the autophagy extracellular vesicles can more effectively infect brain and spleen tissue of a mouse, so that the autophagy extracellular vesicles can be used for treating the brain and spleen tissue of the mouse; therefore, the autophagy extracellular vesicle disclosed by the invention can break through the limitation of a host virus specific receptor, efficiently infect corresponding tissues and enlarge the virus tissue tropism. Therefore, the autophagy extracellular vesicle disclosed by the invention can be used for screening antiviral drugs, and also has important significance for constructing a virus infected animal model.
Owner:SUZHOU UNIV

Composition and essence lotion with whitening and skin tendering effects as well as preparation method and application of composition and essence lotion

The invention relates to a composition with whitening and skin tendering effects, essence lotion and a preparation method and application of the essence lotion, in the composition with the whitening and skin tendering effects, the weight ratio of achillea millefolium extract to hydroxyethyl piperazine ethanesulfonic acid to ormosia henryi bark extract is (0.1-1): (0.5-8): (0.05-0.5). The essence lotion is prepared from the following components in percentage by weight: 0.75 to 6 percent of composition with skin whitening and tendering effects, 3 to 8 percent of emollient, 0.5 to 2 percent of emulsifier, 0.01 to 1 percent of filler, 0.5 to 2 percent of thickener, 0.8 to 1.5 percent of preservative, 0.02 to 0.2 percent of daily essence, 0.1 to 10 percent of skin conditioner, 0.1 to 10 percent of humectant and the balance of deionized water. The main components have a synergistic effect, can effectively regulate and control the information network effect of endothelin and reduce the differentiation, proliferation and the like of melanocytes in the first step of melanin generation by inhibiting the activity of tyrosinase, can promote cell autophagy and effectively metabolize melanin and lipofuscin generated in the skin, and achieves the effects of whitening, whitening, whitening and the like. The skin tendering effect is realized.
Owner:MAGELINE BIOLOGY TECH CO LTD

Marine ecological restoration effect evaluation system based on unmanned aerial vehicle remote sensing quantification

The invention discloses an unmanned aerial vehicle remote sensing quantitative marine ecological restoration effect evaluation system, and relates to the technical field of marine ecological monitoring and evaluation, and the system comprises a rhythm resonance excitation module, a resonance coupling inversion module, an error autophagy verification module, and a resonance steady state adjustment module. According to the invention, a three-in-one framework of a rhythm resonance coupling mechanism, an error autophagy verification mechanism and a rhythm phase latch-cross-scale energy anchoring stator mechanism is utilized, and four core modules of rhythm resonance excitation, resonance coupling inversion, error autophagy verification and resonance steady state adjustment are combined. The method solves the problems of low evaluation precision, no self-verification capability and large errors caused by marine environment interference due to manual sampling recheck and rhythm splitting in the prior art, realizes quantitative evaluation and self-verification of the marine ecological restoration effect without manual sampling, remarkably improves evaluation efficiency, credibility and precision, and is suitable for large-scale popularization and application. And micro-scale power data can be synchronously output, the endurance of the unmanned aerial vehicle is prolonged, and the restoration trend is pre-judged.
Owner:FIRST INSTITUTE OF OCEANOGRAPHY MNR

Chloroquine lipid, preparation method and application thereof, and lipid nanoparticles containing chloroquine lipid

The invention relates to a biological medicine technology, and discloses chloroquine lipid, a preparation method and application thereof, and lipid nanoparticles containing the chloroquine lipid. The chloroquine lipid is synthesized from chloroquine substances and alkylene oxide through a ring-opening reaction, and the chloroquine substances are selected from at least one of chloroquine, hydroxychloroquine, chloroquine derivatives and hydroxychloroquine derivatives. The lipid nanoparticles contain the chloroquine lipid, cationic lipid, phospholipid, PEG (polyethylene glycol) lipid and cholesterol. The chloroquine lipid can be used as a lipidated autophagy inhibitor, can endow the LNPs carrier with an autophagy inhibition function, and realizes the autophagy inhibition effect of'time-space synchronization ', so that the obstacle of'autophagy lysosome degradation' is broken through, and the gene delivery efficiency is enhanced.
Owner:BEIJING INST OF TECH +1

Application of cassava common mosaic virus CP in down-regulation of MeGRXC3

The invention provides an application of a CP gene, or a protein encoded by the CP gene, or a recombinant vector or host bacteria containing a CP gene coding region in down-regulation of the MeGRXC3 expression level. Researches find that CP and MeGRXC3 interact with each other, so that the growth ability of yeast in an SD / -Leu / -Trp / -His / -Ade auxotrophic culture medium can be improved, cell autophagy can be activated, the expression of MeGRXC3 can be down-regulated, and the active oxygen content of plant tissues co-expressed with MeGRXC3 can be increased. Research results lay a theoretical foundation for breeding of common cassava mosaic virus disease resistance.
Owner:SANYA RES INST OF CHINESE ACAD OF TROPICAL AGRI +1

Ergothioneine anti-aging skin care composition and preparation method thereof

The invention belongs to the field of cosmetics, and particularly discloses an ergothioneine anti-aging skin care composition and a preparation method thereof. According to the formula, each 100 g of the anti-allergy anti-inflammatory and anti-allergy anti-allergy anti-allergy anti-allergy anti-allergy anti-allergy anti-allergy anti-allergy anti-allergy anti-allergy anti-allergy anti-allergy anti-allergy anti-allergy anti-allergy anti-allergy anti-allergy anti-allergy anti-allergy anti-allergy anti-allergy anti-allergy anti-allergy anti-allergy anti-allergy anti-allergy anti-allergy anti-allergy anti-allergy anti-allergy anti-allergy anti-allergy anti-allergy anti-allergy anti-allergy anti-allergy anti-allergy anti-allergy anti-allergy anti The transdermal rate and the stability of the ergothioneine and the pyrroloquinoline quinone are improved by adopting a liposome encapsulation technology, an'enzymatic + non-enzymatic 'dual-mode antioxidant system is formed by combining the French muskmelon extract and the roxburgh rose extract, full-type free radical scavenging is covered, and cell autophagy is regulated and controlled through spermidine to delay senescence.
Owner:YIKANG INTERNATIONAL CO LTD

Ultrasonic therapy system and use thereof

PCT designated stage expiredWO2025152115A1Ultrasound therapyAutoimmune conditionAutoimmune disease
Disclosed in the present invention are an ultrasonic therapy system and use thereof. The ultrasonic therapy system comprises a host and a therapy head. The host comprises a signal module, a power supply module, an output module, and a matching module. The therapy head comprises a piezoelectric module and an amplitude transformer module. The length of the piezoelectric module and the length of the amplitude transformer module are half of the wavelength. The output frequency range of the ultrasonic therapy system conforms to the frequency range of ultrasonic waves output by bats. According to the present invention, low-frequency low-intensity ultrasonic acts on the immune system of an organism, and specific immune environments featuring high interferon α expression, strong immune response, enhanced autophagy, down-regulated inflammation level, etc., are formed in the organism. Therefore, the ultrasonic therapy system can be used to resist tumors and viruses, prevent and ameliorate inflammatory aging, prolong the lifespan, and treat autoimmune diseases.
Owner:SHANGHAI A&S SCI TECH DEV CO LTD

Autophagy activator, hyaluronic acid production promoter, and antioxidant

A novel autophagy activator is provided. An autophagy activator, a hyaluronic acid production promoter, and an antioxidant, each of which contains a lactic acid fermentation product obtained by fermenting a raw material derived from a tea tree with lactic acid bacteria.
Owner:OTTO FAGICO CO LTD

Magnetic-aptamer targeting tumor tissue nano-drug delivery system as well as preparation method and application of magnetic-aptamer targeting tumor tissue nano-drug delivery system

The invention discloses a magnetic-aptamer targeting tumor tissue nano-drug delivery system as well as a preparation method and application thereof, and belongs to the field of medicines. The system comprises a mesoporous ferroferric oxide magnetic core, a polyethyleneimine (PEI) layer coated outside the mesoporous ferroferric oxide magnetic core and an aptamer adsorbed outside the PEI layer, and an autophagy activator can be selectively loaded in the mesoporous core. The preparation method comprises the following steps: sequentially carrying out drug loading, PEI coating and aptamer modification on the mesoporous Fe3O4 nanoparticles. According to the invention, efficient enrichment and endocytosis of tumor tissues are realized through dual effects of magnetic targeting and active targeting of the aptamer; lysosome escape is promoted by using the proton sponge effect of PEI; finally, by virtue of the synergistic effect of iron ions released by degradation of the Fe3O4 nanoparticles and endogenous iron ions released by ferritin autophagy induced by an autophagy activator, ferroptosis of tumor cells is induced through enhanced Fenton-like reaction, so that high-efficiency and low-toxicity targeted therapy is realized.
Owner:YANSHAN UNIV

Application of compound D25

The invention belongs to the technical field of biological medicine, and relates to application of a compound D25, in particular to application of a small molecule compound D25 in preparation of a product for preventing or treating Alzheimer's disease (AD), and the structural formula of the compound is shown in the specification. Experiments prove that the small molecule compound D25 can pass through a blood brain barrier, can induce autophagy, can relieve pathological characteristics of an AD mouse model and improve cognitive impairment of the AD mouse model, can reduce the proportion of disease-related microglial cells by recovering the morphology of the microglial cells and improving the A beta phagocytosis capacity of the microglial cells, has the potential of promoting neuronal growth and increasing the number of protrusions, and can be used for preparing a medicine for treating the disease-related microglial cells. Therefore, AD can be effectively treated, the safety is high, the effect is achieved, and the application prospect is great.
Owner:KUNMING INST OF ZOOLOGY CHINESE ACAD OF SCI +1

Compositions for improving physiological function with age

Provided are methods for treating a disease or condition associated with reduced autophagy in a patient, which includes administering to the patient, either simultaneously or sequentially, a therapeutically effective amount of a synergistic combination of compounds from at least two and preferably three of the classes of compounds selected from a saccharide, a vitamin, a ketone body, a polyphenol, and a methylxanthine. The compounds may be present in a subtherapeutic effective amount relative to the compound's dosing when given as a single agent. Also provided are pharmaceutically acceptable compositions and kits including at least two and preferably three of the named classes of compounds.
Owner:THE REGENTS OF THE UNIVERSITY OF COLORADO

Application of rapamycin in preparation of composition for treating hereditary spasmodic paraplegia SPG subtype

The invention discloses an application of rapamycin in preparation of a composition for treating a hereditary spastic paraplegia SPG subtype. The rapamycin can obviously improve the motion disorder and pathological injury phenotype of an SPG80 subtype mammal model, improve the lysosome function and promote the autophagy process through mTOR inhibition, provides specific intervention for nerve cell apoptosis and a glial cell abnormal activation mechanism caused by UBAP1 deletion, fills the blank that no effective treatment means exists for the SPG subtype, and has a good application prospect. A theoretical basis is provided for clinical treatment of patients, and a reference is provided for other SPG variations (such as SPG3A).
Owner:FUJIAN MEDICAL UNIV

A granule of anti-liver cancer special medical food based on multi-target point synergy and a preparation method thereof

PendingCN122271519AImprove bioavailabilityInhibit apoptosisBiotechnologyNutrition
This invention discloses a multi-target synergistic anti-liver cancer medical food granule and its preparation method. The granule uses medicinal and edible homologous foods and novel resource foods as raw materials, and is composed of curcumin extract, esterified fat-soluble EGCG, Moringa leaf powder, yeast β-glucan, Astragalus extract, Schisandra extract, Salvia miltiorrhiza extract, Poria cocos powder, resistant dextrin, and erythritol in a specific ratio to construct a three-dimensional synergistic system of "direct killing-immune regulation-liver protection," which can induce ferroptosis in liver cancer cells, inhibit protective autophagy, activate the body's immunity, and protect liver cells. This invention employs directional extraction, multi-layer coating, and high-pressure fusion granulation technology. Nanoparticle liposome encapsulation, esterification modification, and pH-responsive enteric coating improve the stability and bioavailability of the components, solving the problems of poor water solubility, low absorption, and easy degradation of natural active ingredients. The granule has clear efficacy, high safety, and stable process, and can be used as a medical food for adjuvant therapy and nutritional support during the recovery period of liver cancer.
Owner:YUNNAN HUANGJIA MEDICAL CIRCLE INST OF TRADITIONAL CHINESE MEDICINE

New target for researching lung cancer occurrence and development of obese lung cancer patient and application of new target

The invention relates to the technical field of molecular biology and oncology, and particularly discloses a new target spot for researching lung cancer occurrence and development of obese lung cancer patients and application of the new target spot. The relationship among an overexpression candidate, an autophagy marker, a blood biochemical characteristic and an obesity inducing related index is discussed by researching the correlation between the serum candidate level of a lung cancer patient and the growth and migration of cancer cells in vitro and researching the correlation between autophagy change of a lung cancer mouse and obesity. According to the application, candidate genes related to lung cancer and obesity are FAM19A5 and MFGE8, and a lung cancer cell line in which the candidate genes FAM19A5 and MFGE8 are over-expressed is established, so that the FAMA19A5 and MFGE8 can mediate lung cancer cell migration through SPHK1 / S1PR1 / AKT / ERK, and autophagy is regulated and controlled through an SPHK1 / S1PR1 / AKT / ERK signal channel to promote lung cancer development.
Owner:QUANZHOU HI Q BIOMEDICAL LABOTATORY CO LTD

Stable transfection cell strain for evaluating fibroblast autophagy flux as well as construction method and application of stable transfection cell strain

The invention discloses a stably transfected cell strain for evaluating fibroblast autophagy flux and a construction method of the stably transfected cell strain. The construction method comprises the following step: infecting fibroblasts by using HBAD (Hepatitis B Antigen)-red fluorescent protein-EGFP-LC3 autophagy double-labeled adenovirus. The construction method can be combined with a super-resolution microscope to dynamically observe the autophagy intensity change in the primary fibroblasts through an imaging method.
Owner:博溪生物科技(苏州)有限公司

Autophagy derivative

To provide a skin-whitening agent, autophagy derivative, and epidermis hyperplasia inhibitor.SOLUTION: Provided are a humus extract containing fulvic acid and mineral, and / or a skin-whitening agent including uncoupler other than fulvic acid, an autophagy derivative including uncoupler in keratinocyte, and an epidermis hyperplasia inhibitor including uncoupler.SELECTED DRAWING: None
Owner:STYLE & VALUE JAPAN INC